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Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons
R E Peterson1, H M Theobald, G L Kimmel
1School of Pharmacy, University of Wisconsin, Madison 53706.
Abstract:
Developmental toxicity to TCDD-like congeners in fish, birds, and mammals, and reproductive toxicity in mammals are reviewed. In fish and bird species, the developmental lesions observed are species dependent, but any given species responds similarly to different TCDD-like congeners. Developmental toxicity in fish resembles "blue sac disease," whereas structural malformations can occur in at least one bird species. In mammals, developmental toxicity includes decreased growth, structural malformations, functional alterations, and prenatal mortality. At relatively low exposure levels, structural malformations are not common in mammalian species. In contrast, functional alterations are the most sensitive signs of developmental toxicity. These include effects on the male reproductive system and male reproductive behavior in rats, and neurobehavioral effects in monkeys. Human infants exposed during the Yusho and Yu-Cheng episodes, and monkeys and mice exposed perinatally to TCDD developed an ectodermal dysplasia syndrome that includes toxicity to the skin and teeth. Toxicity to the central nervous system in monkey and human infants is a potential part of the ectodermal dysplasia syndrome. Decreases in spermatogenesis and the ability to conceive and carry a pregnancy to term are the most sensitive signs of reproductive toxicity in male and female mammals, respectively.
Insights
TCDD-like compounds cause developmental toxicity in fish, birds, and mammals, and reproductive issues in mammals. Functional alterations, like reproductive and neurobehavioral effects, are the most sensitive indicators of toxicity.
Area of Science:
- Environmental toxicology
- Comparative toxicology
- Developmental and reproductive toxicology
Background:
- TCDD-like compounds are environmental contaminants with known toxic effects.
- Understanding their impact on development and reproduction across species is crucial for risk assessment.
Purpose of the Study:
- To review developmental toxicity of TCDD-like congeners in fish, birds, and mammals.
- To review reproductive toxicity of TCDD-like congeners in mammals.
- To identify sensitive endpoints for developmental and reproductive toxicity.
Main Methods:
- Literature review of studies on TCDD-like congener toxicity.
- Comparative analysis of species-specific responses.
- Identification of sensitive developmental and reproductive endpoints.
Main Results:
- Developmental toxicity varies by species but congener responses are consistent within species.
- Fish exhibit "blue sac disease"; birds show malformations.
- Mammalian developmental toxicity includes growth reduction, malformations, functional alterations, and mortality, with functional alterations being most sensitive.
- Reproductive toxicity in mammals includes decreased spermatogenesis and impaired fertility.
Conclusions:
- Functional alterations are the most sensitive indicators of developmental toxicity in mammals.
- Ectodermal dysplasia syndrome, affecting skin, teeth, and potentially the central nervous system, is observed in humans and animals exposed to TCDD-like compounds.
- Decreased spermatogenesis and fertility are sensitive endpoints for reproductive toxicity in mammals.